In the first year of this research, we have established the in vitro conditions necessary for the cell culture of human non-Hodgkins malignant lymphomas (NHL) and their sensitivity to various human lymphoid growth factors. These studies principally involved evaluating the proliferative capabilities of human malignant non-Hodgkin's lymphomas (NHL). Our hypothesis was that these neoplastic cells from these tumors, which resemble normal lymphoid cell counterparts, could proliferate in response to normal lymphoid growth factors (T-cell growth factor [TCGF] or B-cell growth factor [BCGF]). We felt that this proliferative capability indicates that the neoplastic cells can be regulated by the immunoregulatory molecules (lymphokines and monokines) made by infiltrating or indigenous accessory cells (T cells and macrophages) invariably present in lymphomatous lesions. To date, we have studied 36 patients with NHL of a wide spectrum of histopathological subtypes, including small cell (WDL, N-PDL, mixed cell) and large cell ("histocytic," immunoblastic, etc.) types. These tumors have included both T-\and B-cell-type NHL. In these studies, we have used the Human Malignancy Associated Nucleolar Antigen (HMNA), which we have shown to be highly efficacious in discriminating between normal and neoplastic lymphoid cells, to verify that the cells being assayed actually represented the tumor cells. In the next 12 months, we will attempt to establish long-term lines from the tumor cells and from the normal accessory cells that are found in the lymphomatous lesions and which we believe are the cellular sources of the growth factors utilized by the malignant cells. These cell lines should allow us to study the various immunoregulatory interactions that occur in malignant lesions, probably through the mediation of soluble factors such as the interleukins. In addition to proliferative studies, we also will be looking into factors that can mediate differentiation in the lymphoma cells to Ig-secreting cells in the B-cell type or the production of effector molecules in the T-cell type. Cell sorting and flow cytometry also will be used for better quantitative definition of the cells involved. These studies should further develop the in vitro systematic study of immunoregulation in the NHL, which is the major goal of this project.